Farfel Z, Mayan H, Yaacov Y, Mouallem M, Shaharabany M, Pauzner R, Kerem E, Wilschanski M
Department of Medicine, Tel Aviv University, Tel Aviv, Israel.
Eur J Clin Invest. 2005 Jun;35(6):410-5. doi: 10.1111/j.1365-2362.2005.01504.x.
WNK [With No K (lysine)] kinases are essential for regulation of blood pressure and potassium homeostasis. WNK4 expression was recently found not only in the distal nephron but also in chloride-transporting epithelia. To establish a physiological role for this distribution we studied patients with familial hyperkalaemia and hypertension (FHH), [pseudohypoaldosteronism type II (PHAII)], which is caused by mutations in WNK4.
Measurement of nasal potential difference (NPD) and sweat electrolytes were performed in controls, in six subjects with FHH and ten subjects with cystic fibrosis (CF).
Basal NPD was higher in FHH compared with controls (n = 20): 22.8 +/- 5.7 vs. 16.2 +/- 5.3 mV, respectively (P = 0.014). Maximal response to amiloride was also higher in FHH compared with controls: 14.8 +/- 3.5 vs. 10.0 +/- 4.8 mV, respectively (P = 0.03). In CF these values were 42.9 +/- 9.3 and 29.9 +/- 7.4 mV, respectively. The kinetics of the amiloride effect were faster in FHH, and as first reported here also in CF, compared with controls. At 30 s, amiloride-inhibitable residual PD in FHH was 50 +/- 30 vs. 81 +/- 9% in controls (P = 0.0003) and 56 +/- 7% in CF. The response to chloride-free and isoproterenol solutions, which determines chloride transport activity, was similar in FHH compared with controls [16.0 +/- 8.6 vs. 10.4 +/- 5.9 mV (P = 0.08)]. Sweat conductivity in FHH was 49.7 +/- 7.3 vs. 38.2 +/- 8.1 mmol (NaCl eq) L-1 in 16 controls (P = 0.007) and 94.0 +/- 19.3 in CF.
Mutant WNK4 increases Na+ transport in airways, and therefore it is regulated by wild-type WNK4. This may be caused by a regulation of ENaC or a K+ channel.
WNK（无赖氨酸）激酶对于血压调节和钾离子稳态至关重要。最近发现WNK4不仅在远端肾单位表达，还在氯离子转运上皮细胞中表达。为了确定这种分布的生理作用，我们研究了患有家族性高钾血症和高血压（FHH）[II型假性醛固酮增多症（PHAII）]的患者，该病由WNK4突变引起。
对对照组、6名FHH患者和10名囊性纤维化（CF）患者进行鼻电位差（NPD）和汗液电解质测量。
与对照组（n = 20）相比，FHH患者的基础NPD更高：分别为22.8±5.7 mV和16.2±5.3 mV（P = 0.014）。FHH患者对氨氯吡咪的最大反应也高于对照组：分别为14.8±3.5 mV和10.0±4.8 mV（P = 0.03）。在CF患者中，这些值分别为42.9±9.3 mV和29.9±7.4 mV。与对照组相比，FHH患者以及如本文首次报道的CF患者中，氨氯吡咪作用的动力学更快。在30秒时，FHH患者中氨氯吡咪可抑制的残余电位差为50±30%，对照组为81±9%（P = 0.0003），CF患者为56±7%。FHH患者与对照组相比，对无氯溶液和异丙肾上腺素溶液的反应（可确定氯离子转运活性）相似[16.0±8.6 mV对10.4±5.9 mV（P = 0.08）]。FHH患者的汗液电导率为49.7±7.3，16名对照组患者为38.2±8.1 mmol（NaCl当量）L-1（P = 0.007），CF患者为94.0±19.3。
突变型WNK4增加气道中的Na+转运，因此它受野生型WNK4调节。这可能是由ENaC或钾离子通道的调节引起的。
